Search PubMed⌕ Search

Biomedical subjects

B Lind

Publications and source records attributed to B Lind.

At least 19 recordsLinked to original sources
PubMed1995

Dithiocarbamates induce apoptosis in thymocytes by raising the intracellular level of redox-active copper.

Dithiocarbamates are metal-chelating compounds that can exert either pro-oxidant or antioxidant effects in different situations. They have recently been found to potently inhibit apoptotic cell death, an activity attributed to their antioxidant action. However, when thymocytes were exposed to pyrrolidine dithiocarbamate, an oxidation of the glutathione pool occurred within 90 min. Longer incubation resulted in cell shrinkage, chromatin fragmentation, glutathione depletion, and eventual cell lysis, which is typical of apoptosis in these cells. These changes were inhibited by inclusion of non-permeable metal chelators in the incubation medium, suggesting that pyrrolidine dithiocarbamate exerts its toxic effect by transporting a redox-active metal into the cell. This was directly confirmed when sustained 8-fold elevations of intracellular copper were detected after addition of pyrrolidine dithiocarbamate. In agreement with this, supplementation of the incubation medium with submicromolar concentrations of copper significantly potentiated pyrrolidine dithiocarbamate toxicity. We conclude that pyrrolidine dithiocarbamate exerts a powerful pro-oxidant effect on thymocytes due to its ability to transport external redox-active copper into cells. The resulting increase in glutathione disulfide may also explain the temporary anti-apoptotic activity of this compound described in other systems.

Animals↗
PubMed1995

Spinal nerve root compression.

The pathophysiology of sciatica is not completely understood, although our understanding of its causes is increasing. Mechanical alterations combined with inflammatory changes lead to pain. Compression alters nerve root conduction and compromises the nutritional support of spinal nerve roots (through intrinsic and extrinsic vascularity and cerebral spinal fluid percolation). Mechanical forces can lead to intraneural damage and functional changes in nerve roots. Chemical and metabolic effects can create an inflammatory response. Varying causes of inflammation coupled with varying degrees of compression can occur anywhere along the cauda equina or spinal nerve root, including the dorsal root ganglia, and contribute to the pain response and neurologic deficits associated with sciatica.

Animals↗
PubMed1995

Mutations at the C-terminal isoleucine and other potential iron ligands of 5-lipoxygenase.

The non-heme iron centre in human 5-lipoxygenase was studied. Recombinant enzyme was expressed in Escherichia coli, purified and assayed for iron content and enzyme activity. For non-mutated enzyme, the iron content was 1.01 +/- 0.19 mol/mol. Deletion of the C-terminal Ile673 resulted in an iron content of 0.03 +/- 0.07 mol/mol and undetectable lipoxygenase activity. Mutations at His367, Glu376 and Asn554 led to drastically decreased enzyme activity (< 2% of non-mutated control) but iron was still present. In addition to Glu376, eight other conserved acidic residues (Asp/Glu) in 5-lipoxygenase were replaced, none of which was crucial for enzyme activity. We conclude that Ile673 is an iron ligand in 5-lipoxygenase, while our results do not support that Glu376 or Asn554 have this function. The possible role of His367 as a replaceable iron ligand is discussed.

Arachidonate 5-Lipoxygenase↗
PubMed1995

Selenium concentrations in brain after exposure to methylmercury: relations between the inorganic mercury fraction and selenium.

Three groups of female monkeys (Macaca fascicularis) were exposed to methylmercury (MeHg, p.o. 50 micrograms Hg/kg body wt per day) for 6, 12, or 18 months. One group was exposed to MeHg for 12 months and kept unexposed for 6 months before sacrifice. Another group of three monkeys was exposed to HgCl2 i.v. for 3 months. Total and inorganic mercury concentrations in occipital pole and thalamus were determined by cold vapor atomic absorption spectroscopy. Selenium concentrations were analyzed by hydride generation atomic absorption spectroscopy. The results indicated an association between concentrations of inorganic mercury and selenium in both occipital pole and thalamus in the MeHg-exposed animals. A linear regression model using concentrations of inorganic mercury (nmol/g wet wt) as independent variable, and selenium concentrations (nmol/g wet wt) as the dependent variable showed significant correlations between the variables in both occipital pole and thalamus (r = 0.85 and r = 0.91, P < 0.0001). The intercept of the regression line was slightly lower (about 2 nmol Se/g wet wt) than the selenium concentrations found in control monkeys (about 3 nmol Se/g wet wt). There was a tendency to a "hockey stick"-shaped relationship between concentrations of selenium and inorganic mercury in the thalamus of monkeys with ongoing exposure to MeHg. An important role for selenium in the retention of mercury in brain is indicated.

Animals↗
PubMed1995

Effect of moderate ethanol intake on the heart: biochemical and morphological studies with isolated cardiomyocytes from rats fed a low-protein diet.

OBJECTIVE: It has been shown that chronic consumption of ethanol can impair myocardial function and result in morphological changes of the heart. The purpose of this work was to evaluate relations between changes in energy metabolism and changes of cell morphology. METHOD: Long-term effects of moderate ethanol consumption on the heart were examined in isolated cardiomyocytes from rats fed a pellet with low-protein content for 6 months. Digitonin treatment of the cardiomyocytes was used to separate mitochondrial and cytosolic fractions. RESULTS: A greater fraction of contracted myocytes was isolated from ethanol- and glucose-treated rats, than from rats fed only glucose and/or water as liquid supplement. There were changes of the ultrastructure of myocytes from ethanol and glucose-treated rats, which included mitochondrial degeneration, accumulation of fat droplets and depletion of the glycogen content. An elevated cytosolic level of nucleotides (ATP, ADP and NAD) and disappearance of magnesium from the mitochondrial fraction were observed in myocytes from rats fed ethanol and glucose. The release of adenosine was also found to be inhibited in these cells. CONCLUSIONS: Our results show that moderate ethanol consumption by rats during protein-restricted conditions produces subclinical changes of cardiomyocyte ultrastructure and alteration of cell morphology. Furthermore, the results indicate that changes of the energy homeostasis in myocytes and inhibition of sarcolemmal adenosine transport are early events that appear to precede the histological alterations.

Alcohol Drinking↗
PubMed1995

Six different point mutations in seven Danish families with symptomatic protein C deficiency.

Six different point mutations of the protein C gene are described in seven Danish families with protein C deficiency associated with an increased risk of venous thromboembolism. All affected family members are heterozygotes for the mutated protein C genotype. One mutation is a G2992-->A transition at position +5 in the 5' splice site of intron D. The other five mutations affect the protein coding region. One is a C1432-->T transition in exon III converting the highly conserved Arg15 to Trp in the Gla-domain. Another mutation is a G3157-->C transversion in exon V converting the non-conserved Gly72 to Arg in the epidermal growth factor domain. The remaining three mutations are located in non-conserved amino acid positions in exon IX and affect the serine proteinase domain. The first is a G8559-->C transversion converting Gly282 to Arg. The second is a C8571-->T transition (present in two families) converting Arg286 to Cys. The third is a C8695-->T transition converting Pro327 to Leu. In each family the protein C deficiency cosegregates or probably cosegregates (one family, G8559-->C) with the mutation. All affected family members exhibit a reduction of both the antigen and the functional plasma concentration of protein C to approximately 50% of normal indicating that the mutated protein C is not present (type 1 deficiency) or only present in low amounts in plasma. Agarose gel electrophoresis followed by Western blotting shows that the Arg15-->Trp substitution is associated with a normal as well as an abnormal migrating plasma protein C band.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[Binswanger disease. A blood pressure-related dementia].

Interest in Binswanger's disease has increased during the past decade, owing to the possibility of detecting white matter changes with computerised and magnetic resonance tomography. This paper consists in a summary of clinical symptoms and signs and possible diagnostic criteria, discussion of differential diagnosis, and the presentation of two own cases. Both patients manifested mild dementia and gait disturbance, and one had frequent drop attacks. Severe supra- and infra-tentorial white matter changes were present in both cases. It is important to consider a possible diagnosis of Binswanger's disease, as treatment of the appropriate risk factors may prevent or delay the development of dementia.

Aged↗
PubMed1994

Speciation of mercury in the primate blood and brain following long-term exposure to methyl mercury.

Total (T-Hg) and inorganic (I-Hg) mercury in blood and brain of female Macaca fascicularis monkeys, exposed to daily peroral doses of methyl mercury (MeHg; 50 micrograms Hg/kg body wt) for 6, 12, or 18 months, or to continuous iv infusion of HgCl2 (200 micrograms Hg/kg body wt) for 3 months, were determined. In normal weight monkeys (2.4-4.1 kg body wt) exposed to MeHg, steady state of T-Hg in blood (1.1 micrograms Hg/g) was reached in about 4 months. The elimination T1/2 in blood was 26 days. I-Hg constituted 7% of T-Hg in blood. The average concentration of MeHg in occipital pole and thalamus was about 3 micrograms Hg/g at 6 months and 4.5 micrograms Hg/g at 12-18 months. Accumulation in brain seemed to be biphasic. Following termination of 12 months exposure, elimination T1/2 for MeHg in brain was 35 days. I-Hg constituted about 9% of T-Hg in brain at 6-12 months, 18% at 18 months, and 74% at 6 months after termination of exposure. The I-Hg concentrations were somewhat higher in thalamus than in occipital pole. The elimination T1/2 for I-Hg was extremely long, on the order of years. Most likely, the I-Hg was formed by demethylation of MeHg in the brain. In monkeys exposed to HgCl2, blood levels of 0.6 micrograms I-Hg/g gave rise to brain I-Hg levels of about 0.1 micrograms/g only. In three heavy weight monkeys (5.0-6.1 kg body wt) exposed to MeHg, blood Hg increased to about 2 micrograms Hg/g, indicating a limited distribution of MeHg to fat. The Hg concentrations in brain (7-22 micrograms Hg/g) were considerably higher than those in normal weight monkeys, due to the high blood Hg levels in combination with a high brain-to-blood distribution ratio.

Administration, Oral↗
PubMed1994

Cadmium in blood in Alzheimer's disease and non-demented subjects: results from a population-based study.

Blood cadmium concentrations were studied in Alzheimer's disease (AD) and non-demented subjects. The 29 individuals were randomized from the ongoing population survey on ageing and dementia in Stockholm, the Kungsholmen Project. Smokers had, as expected, higher cadmium levels than non-smokers. Cadmium concentrations in blood were related to diastolic blood pressure in non-smoking, non-demented individuals. In contrast to previous reports no differences in blood cadmium levels were found between AD sufferers and non-demented subjects. Furthermore, there were no correlations between cadmium levels in blood and age or cognitive functions. The importance of quality assurance in sample collection and analysis of cadmium as well as scrutinizing smoking habits is emphasized.

Aged↗
PubMed1994

A pilot study of lead and cadmium exposure in young children in Stockholm, Sweden: methodological considerations using capillary blood microsampling.

A capillary blood microsampling technique was tested among urban young children in Stockholm. Blood lead (BPb) and hemoglobin (Hb) concentrations were determined in capillary blood obtained by fingerstick from 41 children, 13-20 months old, and the accompanying parent. The quality control included control for lead (Pb) and cadmium (Cd) contamination of material and equipment used for blood sampling, washing procedures for the hands and fingers to be punctured, comparisons of Pb and Cd concentrations in blood obtained by fingerstick and by brachial vein puncture from the same individuals, analysis of external quality control samples for Pb and Cd in blood together with the collected samples, and evaluation of the analytical performance using linear regression analysis. The results showed that blood sampling material may contaminate the blood samples with amounts of Pb and Cd that would seriously influence the monitoring results in the low concentration range (< 100 micrograms Pb/L and < 1 microgram Cd/L). However, it is possible to obtain reliable BPb concentrations (> 10 micrograms Pb/L), but not BCd concentrations (< 1 microgram Cd/L), with the capillary blood microsampling technique tested provided that a strict quality control is applied. The sampling procedure tested was well accepted by the children and their parents. The children's median BPb concentration (27 micrograms/L; range 9-73 micrograms/L) was similar to the median BPb concentration of their parents (27 micrograms/L; range 7-74 micrograms/L). However, the correlation between child and parent BPb concentrations was poor (R2 = 0.20), which may indicate different sources to Pb exposure in children and parents.

Adult↗
PubMed1994

Physical disability in older adults: a physiological approach. Cardiovascular Health Study Research Group.

Measures of physical function have been developed primarily to assess health status, prognosis, and service needs. They are now, increasingly, being used as outcome measures in studies seeking to determine the causes of disability. However, the extent to which these standardized measures, as they currently are constituted, are meaningful for the evaluation of underlying pathophysiology is not defined. To assess evidence for an etiologic rationale for these measures, we evaluated self-report of difficulty in physical function in the Cardiovascular Health Study, a study of 5201 men and women 65 years and older in four U.S. communities. We determined (by factor analysis) that self-reported difficulty with each of 17 tasks of daily life aggregates in four groups; i.e. difficulty in one task is associated with having difficulty in the other tasks in the group. These groups include (1) activities primarily dependent on mobility and exercise tolerance; (2) complex activities heavily dependent on cognition and sensory input; (3) selected basic self-care activities; and (4) upper extremity activities. Groups 2 and 3 are similar, but not identical, to Instrumental Activities of Daily Living (IADL) and Activities of Daily Living (ADL), respectively. We then tested whether these groupings were associated with different underlying impairments. Multiple logistic regression analyses indicate that there are constellations of physiologic and disease characteristics significantly (p < 0.01) associated with difficulty in each of these four groups of activities, among 15 chronic diseases and conditions ascertained. Some diseases are uniquely associated with difficulty in one group of tasks; some overlap, and are associated with 2, 3 or 4 groups of tasks. The associations found with difficulty in performing tasks in groups 2 and 3 were frequently stronger than those with the larger groups of ADL or IADL tasks, suggesting increased specificity of associations found with these new groupings. These results suggest that re-grouping of tasks of daily life may provide a more refined physiologically-based outcome measure for use in evaluating causes of disability. The ability to define risk factors for disability may be enhanced by choosing outcome measures with a demonstrated physiologic rationale.

Activities of Daily Living↗
PubMed1994

The role of neuroimaging in the initial management of patients with minor head injury.

STUDY OBJECTIVE: To determine whether omitting neuroimaging in the primary assessment of patients with minor head injuries in the emergency department is safe. DESIGN: Prospective cohort study. SETTING: University hospital, Copenhagen County Hospital, Glostrup, Denmark. PARTICIPANTS: The study group consisted of 2,204 patients presenting to the ED after sustaining minor head injuries. Only patients able to talk and walk were included. MEASUREMENTS AND MAIN RESULTS: The decision to admit was based exclusively on clinical guidelines in which the findings in the ED were of highest priority. Seven patients (0.3%) had a skull radiograph; computed tomography was not used in the primary evaluation. Four hundred thirty patients (19.5%) were admitted. After hospitalization, four patients developed intracranial complications. One required surgery, two required hyperventilation, and one was observed. Follow-up demonstrated that no patient with an intracranial complication had been missed. CONCLUSION: We found it safe to exclude neuroimaging in the primary assessment of patients with minor head injuries in the ED, and to rely instead on clinical criteria.

Adolescent↗
PubMed1993

Splice site mutation in the human protein C gene associated with venous thrombosis: demonstration of exon skipping by ectopic transcript analysis.

Heterozygosity for a G-->C mutation converting the highly conserved Gln184 (CAG) to His (CAC) was identified at the last nucleotide of exon 7 of the protein C gene in two family members with deep vein thrombosis. As the nucleotide is a part of the 5 splice site of intron G, it was examined how the mutation affected splicing of protein C pre-mRNA. Relevant protein C cDNA fragments were amplified with polymerase chain reaction after reverse transcription of ectopic mRNA from peripheral blood lymphocytes. Southern blot analysis and nucleotide sequencing of these fragments showed a fragment (A) corresponding to correctly spliced mRNA originating from the normal allele and a fragment (B) corresponding to a truncated mRNA lacking exon 7, originating from the mutant allele. A third fragment (C) lacking exons 7 and 8 was identified in both affected and unaffected family members, as well as in normal controls. Analysis of human liver protein C mRNA indicated that the ectopic lymphocyte mRNA was qualitatively representative for the tissue-specific mRNA. In conclusion, evidence is provided showing that the mutation abolishes formation of correctly spliced mRNA. This agrees with the observation that the mutation results in a type 1 protein C deficiency.

Adult↗
PubMed1993

The effects of induced hypertension and acute graded compression on impulse propagation in the spinal nerve roots of the pig.

Injuries caused by compression of spinal nerve roots are frequently encountered clinically. Experimental studies show that several different factors affect the pathophysiologic changes that occur after these injuries. However, the effect of hypertension in conjunction with graded compression of spinal nerve roots is yet unclear. A previously established porcine model was employed, in which the spinal nerve roots were exposed and compressed by an inflatable balloon. Impulse propagation across the compressed nerve segment was studied by the recording of efferent and afferent nerve action potentials, and nerve conduction velocity. The systemic blood pressure was increased by administration of Neo-Synephrine hydrochloride (phenylephrine HCl) (Winthrop Pharmaceuticals, New York, NY) and elevated 40 +/- 5 mm Hg above the normal (100 +/- 5 mm Hg), and electrophysiologic baseline values were recorded. The spinal nerve roots were then compressed for 2 hours with either 0 (control), 50, 100, or 200 mm Hg. The balloon was deflated and the nerve roots were allowed to recover for 1.5 hours. Impulse propagation was studied every 15 minutes and hypertension was maintained throughout the experiment. The results showed no significant changes of the efferent and afferent nerve action potentials at 0.50 or 100 mm Hg. At 200 mm Hg, efferent and afferent nerve action potentials decreased rapidly and were almost abolished within 20 minutes of compression. Some but not significant recovery was seen of the nerve impulse. Compared to data from normotensive pigs in an earlier experiment, the current study showed that hypertension significantly decreases the susceptibility of the spinal nerve roots to compression at and below 100 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1993

Iron content of human 5-lipoxygenase, effects of mutations regarding conserved histidine residues.

Recombinant human 5-lipoxygenase was expressed in Escherichia coli and purified to more than 95% homogeneity by ammonium sulfate precipitation and agarose-ATP column chromatography. The specific activity of the purified enzyme was 21-28 mumol/mg, as assessed by the generation of 5-hydro(pero)xyeicosatetraenoic acid. The iron content was analyzed by graphite furnace atomic absorption spectrophotometry for six preparations of the enzyme. The average value of the iron content was 0.86 mol/mol (iron/protein) with a range of 0.74-1.15 mol/mol. All lipoxygenases that have been sequenced contain 6 conserved histidine residues. Mutants of 5-lipoxygenase, with substitutions of these 6 conserved histidines, were purified and analyzed. Mutants H372Q and H550Q had no detectable enzyme activity and were also practically devoid of iron. Three mutants regarding His367 (H367Q, H367N, and H367S) were all inactive but had partial iron contents (0.5, 0.2, and 0.5 mol/mol, respectively). Finally, the mutated proteins H362Q, H390Q, and H399Q displayed reduced enzyme activity but contained similar amounts of iron as non-mutated 5-lipoxygenase. We conclude that histidines 372 and 550 constitute two of the iron ligands in 5-lipoxygenase. Also His367 is necessary for the enzyme activity, but this residue is not crucial for binding of iron.

Arachidonate 5-Lipoxygenase↗